Anaemia can be defined as decreased haemoglobin counts or reduced red blood cell counts or reduced oxygen carrying capacity of blood, due to “loss of” or “abnormality of” red blood cells or haemoglobin.
Normal Heamoglobin Counts
6 months to 5 years of age > 11g/dl
5 years to 12 years of age > 11.5g/dl
12years to 16 years of age > 12g/dl
Adult Females (non-pregnant) > 12g/dl
Adult Females (pregnant) > 11gm/dl
Adult Males > 13g/dl
CAUSES OF ANAEMIA
Excessive Red Blood Cell destruction
Anaemia of Chronic diseases
Autoimmune haemolytic anaemia
Inflamatory bowel diseases
Hypervolemia or water retention due to sodium or other salts.
Genetic hereditary conditions like Thalasemia
Reduced erythropoetin production
Excessive RBC destruction
Impaired RBC production
Certain infections like malaria which causes RBC destruction.
Certain drugs which causes RBC destruction eg. Quinine causes chinchonism.
Bone Marrow lesions and pathologies
CLASSIFICATION OF ANAEMIA
There are many types of anaemias. It can be broadly classified into 7 categories depending upon their causes
Anaemia due to
Impaired or abnormal Erythropoesis
Based on RBC morphology it can be classified into 3 groups
FEW COMMON and RARE TYPES OF ANAEMIA
Iron Deficiency Anaemia
Autoimmune Hemolytic Anaemia
Congenital Dyserythropoetic Anaemia
Anaemia of Prematurity
Erythroblastopenia or Pure Red Cell Aplasia
In children it affects growth in general
Somnolence, Drowziness in day time
Disturbed sleep at night
Pallor, general pale appearance of skin, mucous membranes and eyes.
Dyspnoea on Exertion.
Reduced Immunity, tendency to catch infections and slow recovery and healing.
Cyanosis in severe cases
Low blood pressure
Craving for indigestible things , PICA
Cold clammy extremities
Oedematous swelling of extremities, dependent oedema
Angina or cardiac failure in severe cases
Will impact general growth and repair of all the vital organs and tissue of the body.
HOMEOPATHIC MEDICINES FOR ANAEMIA
Depending upon the cause of anaemia and general constitution of the patient, one of the following medicines may be called for duty by a homeopathic physician.
COVID-19 term is derived from “CO”rona”VI”rus “D”isease 20″19” it is caused due to Novel Coronavirus also known as 2019-nCoV or SARS-CoV-2. It is commonly known as Wuhan Coronavirus or Wuhan Sea Food Market Pneumonia Virus is an enveloped positive sense, single strand, RNA Coronavirus with a neucleocapsid of helical symetry which can infect and spread through human to human transmission causing flu like illness officially termed by WHO as Covid-19 where “Co” represents CORONA, “vi”represents virus, “d” stands for disease and “19” stands for year of first outbreak 2019.
Novel Coronavirus 2019-nCoV or SARS-CoV-2 Classification
Novel Coronavirus belongs to
Phylum -Incertia Sedis
Genus -Beta Corona virus
Sub Genus -Serbecovirus,
Virus -2019nCoV or SARS-CoV-2
Coronavirus strands that affect humans
Coronaviruses infects mammals and birds there are total 7 known strands that infect humans including 2019nCoV, first 2 strands were detected in 1960’s
Human coronavirus 229E (HCoV-229E)
Human coronavirus OC43 (HCoV-OC43)
Human coronavirus NL63 (HCoV-NL63, New Haven coronavirus)
Human coronavirus HKU1
Middle East respiratory syndrome coronavirus (MERS-CoV), previously known as novel coronavirus 2012 and HCoV-EMC.
Novel coronavirus (2019-nCoV). This is the strain that causes COVID-19 disease in humans
The first outbreak of the Novel Coronavirus or 2019nCoV in humans was confirmed and notified to WHO by China on 31/12/2019, when patients from Wuhan province of China were suffering with virus related non specific flu like illness from around 8/12/2019 then later the genome was sequenced to confirm this absolutely new and novel strain of coronavirus 2019-nCoV or SARS-CoV-2
Within three months of first reported case on 8/12/2019 the coronavirus outbreak that had first started from Wuhan in China had now reached more than 66 countries including India, Thailand, Japan, South Korea, Italy, Iran, Germany, Taiwan, Hong Kong, USA, Vietnam, Singapore etc. claiming more than 3100+ deaths of estimated 100000+ infected as on 8/3/2020. The death toll is constantly rising, in subsequent two months that is by 8/6/2020 almost 6.5 million got infected and almost 4lac deaths.
It will take some time to estimate mortality rate but it seems to be around 2%. Old people and people with other pre-existing disease condition are at higher risk of succumbing to death. With increasing death rate rises steeply with upto 50-70% death rate in symptomatic patients above 60 with hypertension or diabetes or other complications.
Most of the initial cases were from Huanan seafood market so epizootic origin is suspected.Outbreak of this particular strain of coronavirus is for the first time, So its new for human immune system. As the time lapses the affected community will start developing certain immunity against it, which will slow down the progress of transmission and epidemic as time lapses. Also with time and better understanding of virus and its epidemic, the health authorities will be more efficient in containing the disease and its epidemic.
There is a split between science community where in a group suggests that it has originated from snake where as other claims that snake cannot be the probable the reservoir and is probably from mammal reservoir mostly the bats as the genome sequencing shows 96% resemblance of bat coronavirus and 2019-nCoV.
It is postulated that homologous recombination of Clad A bat viruses “CoVZC45 and CoVZXC21” with some unknown Beta-CoV may have formed 2019nCoV
Human to human transmission of novel coronavirus was confirmed till mid January And the damage was done till then. The virus had started spreading at pace unmatched by any other disease witnessed in past 100 yrs.
PATHOGENESIS OF COVID-19 or Novel Coronavirus 2019 Infection
Still the pathogenesis is not been clearly understood but data and study results are fast pouring in and now we have some basic understanding about but there are many missing gaps and needs to be understood and filled up soon.
The disease causing agent and its full geneome was sequence in December 2019-January 2020, soon after initial outbreak.It was found that the disease causing agent was a virus which had 70% genomic resemblence to SARS-CoV and 50% genomic resemblence to MERS- CoVand they termed it as Novel Coronavirus 2019 or 2019nCoV or SARS-CoV-2 and disease caused by this virus was termed as COVID-19.
Inoculation of 2019nCoV
From initial studies it seems that 2019nCoV attaches to the receptors of Angiotensin Converting Enzyme 2 (ACE2) through an endocytosis process trigerred with the help of spike protein present on surface envelop of the virus . Which are present good quantity on lymphocytes, macrophages, epithelial linning of respiratory mucosa, lungs alveoli, enodthelium of blood vessels, gastrointestinal tract and are also expressed by vital organ like heart and kidneys, which we see getting affected in this disease.
Multiplication and Spread of 2019nCoV
Virus not only has capability to attach to ACE2 receptors of upper respiratory tract and inoculate the cells but also has capability to actively replicate in upper-respiratory tract tissue which was demonstrated by isolating virus from swabs of upper respiratory tract with presence of Sub-Genomic mRNA (sgRNA) in cells of upper respiratory tract. There is tropism of upper respiratory tract and shedding of virus.
All of the above factors explains us fast and easy transmission of virus even in early stage of disease as compared to SARS-CoV and MERS-CoV.
Virus predominantly infects through upper-respiratory in majority cases and then gradually by 3-4 days it involves lower respiratory tract and then by second week there is wide spread invasion into bloodvessels and major vital organs like heart, kidneys with general viremia.
Immune Reaction Towards 2019nCoV Infection and Its Consequences
Its not only virus that causes damage to system but also the body’s immune response against the virus is causing damage to the body which is observed by excessive production of early proinflamatory mediators like Interlukine 6 (IL6) Tumour Necrosis Factor (TNF) Interlukine 1 (IL1), presence of inflamatory infiltrate in lungs. Reduced blood level of T-Lymphocytes and B-Lymphocytes although direct due to viral attack on these cells but also is attributed to redistritbution by immune respone which is demonstrated by presence of comparative more number of T-cell and B-cells at inflamatory sites.
The Cytokine Storm Postulate
There is much evidence to suggest that the initial immune response driven against virus causes activation of coagulation pathway which results in excessive production of early proinflamatory mediators which accumulate overtime leading to vascular hyperpermeability and micro-coagulations resulting from disturbed procoagulant-anticoagulant axis balance due to overt inflamatory response.
Thrombin, known for its primary role in coagulation by activation of platelets and conversion of fibrinogen to fibrin, also has multiple cellular effects that may enhance inflamatory response through Protinase-Activated Receptors(PARs).
Thrombin production is tightly controlled by negative feedback loops and physiological anti-coagulants like Tissue Pathway Factor Inhibitor, Antithrombin III and Protein 3. Inflamatory process can significantly reduce the concentration of anti-coagulants this deviates the fine balance of axis between procoagulant-anticoagulant balance that causes multiple micro-coagulations disseminated intravascular clots and multiple organ failure.
SIGNS AND SYMPTOMS of COVID-19
It shows symptoms that of severe respiratory tract infection giving rise to pneumonia with some gastrointestinal symptoms like other coronavirus infection, Its symptoms are much related to 2003 SARS Epidemic caused due to SARS-CoV.
Most of the patients remain asymptomatic and never get detected many show mild to moderate symptoms this forms the vast majority.
COVID 19 CLINICAL PRESENTATION
Almost 98% symptomatic cases of 2019-nCoV(Covid-19) infection presents with Fever
Dry Coughing is present in almost 82% of symptomatic cases.
Of all the cases sputum production is seen in 25-30% cases and Hemoptysis in upto 5% of all the cases.
Fatigue is observed in almost 70% cases approaching medical care
Muscle-aches (myalgia) in almost 44% of all the cases.
Headaches in almost 13% of all the cases
Diarrhoea experienced in 10% cases
Vomitting seen in 10% of all the patients
Almost 55% of all the cases will develop shortness of breath after 3-8days of initial general symptoms.
Almost 20% of all the the cases seem to progress into severe disease with respiratory distress symptoms within a day or two of developing shortness of breath.
Few patients go into shock and may develop cardiac arythmias.
Of all the cases less than 5-10%(approx) will die due to complications, mostly those who are elderly children or have other prevailing disease condition like diabetes, cardiac diseases, cancer etc.
X ray shows bilateral Lungs involvement with Ground Glass Opacities.
Leucopenia -Low WBC count especially lymphocytes – lymphopenia.
Window period of 2019-nCoV ranges between 2-14days. It takes 2-14 days for symptoms to appear post exposure to virus. Note the patient of 2019 nCoV (Covid-19) can spread infection to others even during this window period l, that is, even before any symptoms starts appearing after first inoculation of 2019-nCoV into body or even any test to decisively test positive.
After window period is over and the symptoms starts appearing the following pattern is seen in progression of clinical symptoms commonly found in most cases.
DAY 1-2 Initially on first 1-2 days patient will show mild fatigue malaise and heaviness of head with mild rise in temperature, few will show a peculiar symptom of Olfactory loss- loss of taste and smell,
DAY 2-3 Gradually the temperature will increase from 2-3rd day with mild irritation in throat.In many this symptom will stop increasing at this stage and will remain mild symptomatic throughout the course of disease, in rest it will progress with fever exceeding 100F, bodyaches, joint pains, weakness
DAY3-4 Fever continues to relapse with dry cough a very few minority might start showing development of shortness of breath even at this early stage.
DAY4-6 Loose motion is frequently encountered on once or twice between 4th and 6thday(in few minority it has appeared right on day one of initial symptoms) this might bring in weakness and exhaustion in patients and those with high fever may be drained even more by accompanying diarrhoea. Few might go into respiratory distress at this stage.
DAY 7–8 From 7th day onwards in few patients fever starts subsiding a bit but in many it persists and few go into respiratory distress.
DAY 8-9 Now 8th-9th days are important to observe as from here on majority patient’s immune system will develop sufficient immunity and resistance against virus and fight it off from the body and recover. Their fever breaks away and they start feeling better with weakness leaving their body but in few cases there is no recovery at this stage such patients progresses into critical stage either fever continues or breathlessness sets this is when the patient needs be urgently shifted to ICU.
Patients with co-morbidity like Diabetes Mellitus, Cardiovascular or Kidney diseases, Immuno-compromised, Organ failure, Asthma Bronchitis, Chronic Obstructive Pulmonary Disease(COPD),Cancer, Autoimmune diseases, Severe anaemia, etc.
Greater severity of pneumonia at presentation.
Elderly patients – Older the age greater the risk.
Radio-opacities and/or pulmonary infiltrates on X-ray findings
There are two types of testing approach one is direct test and indirect test.
Direct test detects viral protein through Polymerase Chain Reaction PCR it is gold standard test as it amplifies/enhances virus protein to detectable levels and give most accurate results possible as we are directly detecting virus. But it is comparatively more costly and time consuming. Still it’s recomended as rapid antibody tests(indirect tests) that are available till date are too inaccurate to rely.
The other is indirect testing where in we are not directly detecting the virus but we try to find out antibodies formed again 2019-nCoV virus. It is comparatively rapid in nature but not accurate.
Time Line of Sensitivity of various Laboratory Investigations for Covid 19.
Day 0: Infected (innoculation)
Upto Day 5: Onset of symptoms(variable 2-21days, with 11.2days average)
Day 7: IgM positive – (from Day 7 toDay 21)
Day 14: IgG positive
Days 1-28: SARS CoV2 RNA & Antigens will be positive
Day 21: IgM disappears
Day 28: SARS CoV2 RNA & Antigens disappears
Disease Progression, Antibodies, Viral load, and Infectivity
Day 0 -Day 7: Window Period, Asymptomatic, Only PCR positive in this Phase, negligible Viral load on day 0-1 but viral load starts increasing very speedily and within a couple of days patient from mildly infectious on day 0 and 1, becomes considerably infectious and infectivity keeps increasing with each passing and in no time patient becomes highly infectious by the end of this period.
Day 7- Day 21: Symptomatic, both PCR and IgM Positive, Patient is highly infectious.
Day 14- Day 21: Decline Phase, PCR, IgM and IgG positive, Patient is highly infectious.
Day 21- Day 28: Convalescence Phase,IgM negative, IgG positive, PCR on declining count, Patient is still infectious.
After day 28: most of the patients are recovered and also PCR turns negative,so they are not infectious, IgG remains elevated,
PREVENTION OF NOVEL CORONAVIRUS INFECTION DURING TIMES OF COVID-19 PANDEMIC
COVID 19 is caused by 2019-nCoV also called SARS-CoV-2. It is a highly contagious virus. The virus can spread even through casual contacts and proximity.
Current studies suggests that virus can survive on surfaces like glass, plastic, metals etc for may be up to 9days and in fecal material for may be upto weeks of which studies are still going on for confirmation.
It has spread to infect more than 63,00,000 person worldwide within a very short span of just 5months since its outbreak. Time and again most of the types of Coronavirus have proven themselves to have potential to create global pandemic claiming many lives within no time. Looking at the scale of pandemic and potential of 2019nCoV virus to spread very fast and claim lacs of lives in no time has spread panic and concern throughout the world as fast increase in cases of COVID-19 has overwhelmed the healthcare system even of the best country of the world with doctors finding them helpless against the disease and its scale and so almost all the major countries of the world have implimented partial or complete lockdown and social distancing norms to contain and slow down the spread of virus.
Keep distance from infected person, at least 6 feet of distance is recomended
Wear masks in public places
Avoid traveling to area affected with 2019-nCoV epidemic
Quatrantine patients traveling from COVID-19 epidemic regions.
Avoid contact with person known to have came in contact with any person infected with 2019-nCoV or travel history from affected area.
Report any case of cough, cold, fever or symptoms of flu to health authorities found in all the regions where cases of SARS-CoV-2 also called 2019-nCoV is prevailing.
Person staying in affected regions should stay within their home and avoid any public places as much as possible.
While moving out in affected region, wear removable and easily washable overcoats, wear disposable gloves, protective eye wears.
Touching with bare hands to public handle, buttons, walls curtains and other objects in public places in affected region should be avoided.
When in public place, try to prefer option with open air and lesser crowd then in enclosed public premises.
Dont use public transport unless its unavoidable.
Stay away from sewage channels and fecal material.
Prefer food prepared at home that too fully cooked and avoid uncooked raw food.
Avoid gathering and meeting people during times of epidemic.
Avoid hand shakes and close proximity with other people during epidemic.
Maintain healthy lifestyle and nutrition, food rich in Zinc, Iron and Vitamin C is recomended
Keep all rooms highly ventilated.
Sanitize your hands frequently almost every 1-2hours, wash hands at least for 20seconds at a time.
People with long hairs should keep hair in such a way that it doesn’t come in contact with potentially infected objects in public places e.g. handle on seat back on buses and trains.
Eat nutritious food, daily yoga and exercise sufficient exposure to sunlight, timely meal sleep and exercise helps boost health and immunity to prevent and fight the disease.
When and how to use mask correctly is explained and demonstrated in the video below by WHO
HOMOEOPATHIC MEDICINE ARSENICUM ALBUM 30 PREVENTIVE MEDICINE AGAINST CORONAVIRUS DURING COVID -19 PANDEMIC
Expert committee of MINISTRY OF AYUSH, GOVT OF INDIA has identified Arsenicum Album 30 as Genus Epidemicus for immunity enhancement during COVID-19 pandemic and has recomended issuing public notice regarding the same. It has also recomended registered homeopathic practioners of India to suggest identified COVID-19 Genus Epidemicus Arsenicum Album 30 to people as immunity enhancement during the COVID 19 pandemic.
As per Ministry of Ayush, Govt of India Circular:-
Central Council for research in Homeopathy and Ministry of Ayush on its 64th Scientific Advisory Board meeting date 28th January 2020, recomended that Arsenicum Album 30 could be taken as prophylactic medicine against coronavirus infection in following prescribed dose
One Dose of Arsenicum Album 30 on Empty Stomach For 3 Consecutive Days
The Dose Should Be Repeated After One Month Following The Same Schedule.
Other Precautions that needs to be followed during homeopathic medication
Do not eat or drink anything at least for 1 hour after taking medicine. Plain water or milk at room temperature could be consumed during this one hour if required.
Brush Teeth at least one hour before or after taking this doses i.e one hour interval prior and after the dose.
Avoid Uncooked Onion, Uncooked Garlic and Coffee atleast for 5 days when you start medicines.
Homeopathic Medicines Indicated For COVID-19 Novel Coronavirus Infection
As per my view other than basic symptomatic supportive treatment and available regular conventional allopathic treatment, homeopathic medicines can be used in conjunction, as per indication under guidance and observation of both qualified homeopathic physician and allopathic physician.
Few of the Homeopathic medicines that can be useful in treatment of COVID-19 that is SARS-CoV-2 infection also called 2019 novel coronavirus infection are listed below.
Initial stage of fever or first day of symptoms in patients much fear and anxiety. Also this medicine can be used for patients having psychological problems of fear fright and anxiety due to COVID-19 pandemic and lockdown psychological effects.
This remedy may prove useful for heaviness of head, fever and bodyaches in COVID-19
This is wonderful drug used since ages to treat respiratory complaints be it asthma, allergic rhinitis, viral respiratory infections or bacterial respiratory infections. Arsenic is consumed by mountaineers since ages which helps them to survive in higher altitudes in low oxygen environment it shall work well in any stage of Covid 19 infection. Itcan also be brought into service in patirnt with breathlessness and respiratory distress. Arsenicum Album acts not only on respiratory sphere but also gastrointestinal sphere which should cover the sptom of diarrhoea that many Covid-19 patients present along with respiratory and general symptoms. It should work well in Covid 19 patients with weakness where the patient is mentally restless but physically too weak to move.
USE OF ARSENICUM ALBUM AS HOMEOPATHIC GENUS EPIDEMICUS TO ENHANCE IMMUNITY AGAINST CORONA VIRUS DURING COVID-19 PANDEMIC
ARSENICUM ALBUM 30 is being identified as Genus Epidemicus and is suggested by Ministry of Ayush, Government of India under consultation of Central Council For Research in Homeopathy that it could be taken as prophylactic against Coronavirus infection one dose every morning on empty stomach for three consecutive days and same protocol should be repeated after a month of the epidemic still prevails in the region.
Cytokine-Storm is associated with increased capalilary permeability and disemminated intravascular coagulation due to overproduction of early-proinflamatory cytokines causing imbalance in procoagulant-anticoagulant balance causing microcoagualations in complicated cases of COVID19.
Arnica Montana is commonly used medicine in homeopathy to dissolve internal clots by stimulating body’s natural pathways to dissolve clots and in inverse concentration un-homeopathically it is also used to form clots stop to stop bleeding. So Arnica Montana has both the type of effects procoagulant and anticoagulant depending on what concentartion and repetition its uses. So with correct homeopathically succussed dilution and correct posology it may prove useful in such acute life threatening situation condition of sudden cytokine storm which causes dissemminated intravascular coagulations with damaged leaky hyperpermeable capillaries .
This medicine works well in cases who are living in region where days are hot and nights are cold. dry coughing, shortness of breath, fever, body aches, muscle aches are some of the symptoms covered by bryonia in COVID-19 patients. Master Hahnemann recommends bryonia alba in epidemics during summer season affecting respiratory system.
Camphora made from camphor can be used in terminally ill COVID-19 patient with gross signs of circulatory insufficiency, cyanosis, hypoxia and this should be the first medicine brought in immediately administered in cases of sudden collapse. Typically it has to be used in higher potency as recomended by some homeopaths.
Agaricus muscarius typically used in homeopathy for frosbite and cyanosis of extrimities can prove beneficial in terminally ill COVID-19 patients with signs of cyanosis and bluish discolouration of extremities like finger and toes this homeopathic medicine should be called in for service.
crategus oxyacantha may prove of great service in COVID-19 patients having cardiac complaints and high lipid profile having circulatory distress and disseminated intravascular coagulations crategus should be thought of is complimentary and supportive medicine.
Aspidosperma Quebracho successfully used in homeopthic mother tincture form since ages for treatment of acute exacerbations of asthma and cardiac asthma may prove useful in COVID-19 patients that has cardiac complaint and develop Cardiac Asthma.
Antimonium Tartaricum shall prove useful for COVID-19 patients living in region with high humidity near sea-shores works wonders in relieving rattling cough with thick mucous especially in aged.
Kalium Bichromicum is very commonly used medicine in homeopathy which is helpful in getting rid of thick stringy ropy mucous it may prove of great service in COVID-19 cases with accumulation of thick mucous difficult to bring up.
Justicia Adhatoda also known as Vasaka in indian medicine and iss used in Ayurveda since ages. It is a great expectorant if used in lower potency preferably in homeopathic mother tincture form.
Thalasemia is a genetic disorder where in mutation or deletion in any genes responsible to produce globin chain of haemoglobin results in abnormal haemoglobin production.
Normal adult has Haemoglobin A (HbA). HbA is a hetrotetramer of two α globin chains and two β globin chains. In normal humans there are total 4 genes (2pairs) for production of αglobin chain and 2 genes(1 pair) for production of β globin chain. When there is defect in genes producing α globin or β globin chains of heamoglobin it results into thalasemia.
Alpha Thalasemia – Abnormal or dhieficient α globin chain production
Beta Thalasemia – Abnormal or deficient β globin chain production.
Delta Thalasemia – Abnormal or defective delta chain production.
Thalasemia in combimation with other haemoglobinopathies like – Haemoglobin S , Haemoglobin E, Haemoglobin C, Haemoglobin D.
Of the above all types the most common types alpha and beta are discussed below.
Alpha Thalasemia has defective α globulin chain production. Genes responsible to produce α globin chain are situated on chromosome 16. HBA1 and HBA2 genes are responsible for production of α globin chain. Both the genes are acquired from both the parents so total two HBA1 and two HBA2 genes. So, there are two genes acquired from each parent making total 4 genes or two pairs(αα/αα) responsible to produce α globin chain.
Depending upon number of gene deleted the condition is classified into 4 categories
α Thalasemia Silent (1 gene deletion)
α Thalasemia Trait (2 gene deletion)
HbH disease (3 gene deletion)
Hb Bart Syndrome (all 4 gene deletion)
Alpha Thalasemia Silent
Any one gene deletion (-α/αα), one of the two allele not received from one parent. Usually there are no sign of anaemia as the remaining three genes produce sufficient alpha globin chains. Althought they dont show symptoms they are the silent carrier and if married to person with one or more α globin making gene deletion then some of their offsprings will have symptoms, probability and severity of the disease in the offsprings will depend on number of gene deletion in the partner.
Alpha Thalasemia Trait
Any two gene deletion, it can be of two genotypes as descussed below, this type shows mild anaemia symptoms.
Two gene deletion – homologous; one of the two allele not received from each parent(-α/-α).
Two gene deletion- heterologous; both the alleles not received from one parent (–/αα).
Three gene deletion (–/-α) No copy of gene received from one parent and only one of the two copy received from another parent. These causes very low α chain production resulting into excess proportion of β chains causing formation of unstable haemoglobin tetramer made up of 4 β globin chains, instead of two α and two β. This type of haemoglobin with all 4 globin chain of β globin is called HbH which is very unstable. These individuals shows moderate to severe anaemia and other thalasemia related symptoms.
Hb Bart Syndrome
All four gene deletion (–/– )No copy of α chain producing gene received from either of the parent. It is a fatal condition where in there are no α chains produced and results into severe fetal condition called hydrops fetalis. Death ensues soon after birth.
Beta thalasemia has defective β globin chain production. For production of β globin chain there is only one gene acquired from each parent makin it total one pair(β/β) i.e total 2 genes responsible to produce β globin chain. Gene Responsible for production of β globin chain is called HBB and is located on chromosome 11.
Beta Thalasemia Minor
(b/β) One gene received from a parent is altered and the one from other parent is normal.
(-/β) No gene received from a parent and the gene received from another parent is normal.
Beta Thalasemia Intermedia
(b/-) One copy of gene received from a parent altered and one from another parent is absent.
(b/b) Genes received from both the parent are altered.
Beta Thalasemia Major
(-/-) No genes producing β globin chain received from either parent.
SIGNS AND SYMPTOMS
Symptoms and its severity depends upon the above mentioned severity of genotype the individual has few complaints which patient with this disease condition show are mentioned below.
General growth is slow
Complete blood count
HOMEOPATHIC TREATMENT AND INDICATED HOMEOPATHIC MEDICINES FOR THALASEMIA
LYMPHOMA – Malignant neoplasm of lymphoid tissue is called Lymphoma.
They are type of blood cancers where in there is abmormal cell-proliferation of Lymphoid Tissue.
Lymphomas and Leukemias both fall under a broader category “Malignant Neoplasms of Lymphoid and Heamatopoetic Tissue” or cancer of Lymphocytes”. Wherein unlike Leukemias, the term Lymphomas is precisely restricted only to the Tumours of Lymphoid tissue.
Types of Lymphoma
Non Hodgkin Lymphoma
Epstein Barr Virus Infection
Non Hodgkin’s Lymphoma
Human T-Lymphotropic Virus Infection
Exposure to certain Pesticides
SIGN’s AND SYMPTOM’s
Pel-Ebstein Fever – Intermittent Fever of around 38C lasting for 1-2weeks and relapsing again after days to weeks
Weight loss of more than 10% within 6 months.
Profuse perspiration especially at night.
Anorexia – loss of appetite
Weakness and fatigue
Dyspnoea on slightest exertion
Ann Arbor Staging System
StageI – Single Lymphnode and surrounding area involved
StageII – Two areas involved a lymph node and another area and both are on the same side of daiphram either above or below
StageIII – Affected areas on both the sides of daiphram with one organ or region near lymphnode or spleen
StageIV – Diffused and disseminated with more than one Extra-Lymphatic organ involved incliding Liver, Bone Marrow, nodular involvement of Lungs.
A or B – type symptom – When patient has following three constitutional symptoms then patient is categorised into B-type symptoms 1) Pel-Ebstein Fever. 2) Weight loss and 3)Night Sweats. When there are no above mentioned combination of B-type constitutional symptoms present then patient is categorised into A type.
“S ” – Disease with Slpeen involvement is denoted with S modifier.
” E” – When disease involves extranodal region that is region surrounding the lymphnodes it is denoted with E modifier.
“X” – X is denominated when the largest bulky deposit region is more than 10cm or if more 35% area of chest is occupied by mediastenum on X-Ray.
Nature of Stage
Clinical Staging “C.S.” – C.S. Mentioned when staging is done based on clinical examination and test.
Pathological Staging “P.S.” – When Staging is done based on pathological findings through invasive techniques like surgical excision etc its Mentioned as P.S.
Biopsy of Lymph node to confirm Lymphoma.
Further to classify Lymphoma:
Fluorescence in-situ Hybridisation.
CT scan and PET scans helps us evaluate extent of spread of the condition and its staging.
HOMEOPATHIC MEDICINES FOR HODGKIN’s LYMPHOMA and NON- HODGKIN’s LYMPHOMA
Abnormal proliferation of blood cells due to defective medullary heamatopoetic stem cells is called leukemia.
In Layman terms, defective bone marrow causes uncontrolled multiplication and abnormal growth of cells that are components of blood causing blood cancer.
TYPES AND CLASSIFICATION
Based on speed of progression and maturity level of most cells most of the Leukemia can be categorised into
Acute – Fast progressing takes weeks to few months, Most of the cells are blast cells (immature cells), Requires immediate treatment, Commonly seen in children.
Chronic – Relatively slow progressing takes months to years, has relatively mature cells, patient usually inder observation before commencing any aggressive treatment, Common in elderly people.
There are some leukemia which do not follow fixed pattern also presentation of symptom may vary in different individual and also there are cases where in they change the classical course of and speed of progression.
Based on types of cells involved, most of the Leukemia can be categorised into
Lymphoid (Lymphocytic) – Precursors of Lymphocytes are involved. It is further classified as per which lymphocytes are involved wether B-cells or T-cells.
Myeloid(Non-Lymphocytic) – Precursors of RBC, Non-Lymphocyte WBC and Platelets are involved.
A Lymphoid or Myeloid leukemia can Either Acute or Chronic as described below
Acute – Lymphoblastic(ALL)
Chronic – Lymphocytic (CLL)
Acute – Myeloid (AML)
Chronic – Myeloid (CML)
Acute Lymphoblastic Leukemia (ALL) –
When there are multiple mutations in the locus, that control cell proliferation, cell maturation and cell death of precursor cells of Lymphocytes called Lymphoblast then this results in ALL. ALL can be of T cell type or B cell type.
Genes associated with ALL –
KMT2A – Infant ALL – onset before 10yr of age
PAX5 – Inherant Autosomal Dominant
ETV6 – Inherant Autosomal Dominant
Certain syndromes that increases risk of ALL
Neurofibromatosis Type 1
Paroxysmal Nocturnal Heamoglobinuria
Severa Combined Immunodeficiency
Schwachmann Daimond Syndrome
SUBTYPES OF ALL
Precursor B-cell ALL
Precursor T-cell ALL
Mature B-cell ALL(also called Burkitts Leukemia due to its similarity with Burkitts Lymphoma)
Acute Biphenotypic Leukemia.
Acute Myeloid Leukemia (AML)
It is an acute Non-Lymphocytic type of malignanacy which involves myeloblast cells(precursor of monocytes and granulocytes).
In AML there is mutation of genes that mature and differentiate the myeloblast cell will arrest maturation and differentiation and the cell will freeze in undifferentisted immature state and when this type of mutations combined with mutations in genes controlling proliferation in same cell will result in clonning of immature undifferentiated cells resulting in AML
Genes associated with AML
Subtypes of AML
Subtypes of AML are classified based on staging of maturation i.e. at which stage the msturation of the cell is arrested and how is the general behaviour of cells and which genes are involved.
Undifferentiated Acute Myeloblastic Leukemia
Acute Myeloblastic Leukemia with Minimal Maturation
Acute Myeloblastic Leukemia with Maturation
Acute Pro-Myelocytic Leukemia (APL)
Acute Myelomonocytic Leukemia
Acute Myelomonocytic Leukemia with Eosinophilia
Acute Monocytic Leukemia
Acute Erythroid Leukemia
Acute Megakaryoblastic Leukemia
Adult T-Cell Leukemia
Blast Crisis of CML
Chronic Lymphocytic Leukemia (CLL)
B-cell Pro-Lymphocytic Leukemia(B-PLL)
T-Cell Pro-Lymphocytic Leukemia(T-PLL), T-PLL doesnt completely fit into this category.
Large Granular Lymphocytic Leukemia(LGLL)
Chronic Myeloid Leukemia (CML)
Chronic Granulocytic Leukemia
Chronic Neutrophillic Leukemia
Chronic Myelo-Monocytic Leukemia(CMML)
Atypical CML (aCML)
Chronic Eosinophillic Leukemia
Few other types, preleukemias and syndromes that cannot be classified in above category
Other Myelodysplastic Syndromes
Leukemia is caused due to mutations in genes that are associated with proliferation, differentiation, growth, maturation and cell death of blood cells. With different types of mutations responsible for different types of leukemia.
These genetic mutations can be inherited or acquired due to multiple reasons of which few known risk factors are
Exposure to certain chemicals (e.g. benzene, petrochemicals, hair-dyes, agent orange herbicide, certain insecticides)
Radiation – ionising radiations and doubtedly non-ionising radiations too.
Smoking and tobacco use.
Prior alkylating chemotherapy for some other form of malignancy.
Viruses – Human T-cell Lymphotropic Virus – 1 HTLV-1 is associated with Adult T-cell Leukemia and Hepatitis C is associated with CLL
Diseases and Syndromes – Down’s Syndrome, Kline Felter syndrome, Fanconi Anaemi, Ataxia-Telangiectasia or Louis-Bar Syndrome, Myelodysplastic syndrom, Myeloproliferation syndrome.
Few of these factor are seen responsible for specific type of cancer (eg HTLV1 causes Adult T-cell Leukemia, Tobacco and Down’s Syndrome increases risk of AML).
SIGNS AND SYMPTOMS
Symptoms may vary in different types of leukemia, different individuals and different stages of disease.
Paleness due to anaemia
Shortness of breath
Headache, lethargy, stiffness of neck
Loss of appetite
Tendency to catch infection too frequently
Fever usually due to secondary infections
Painful long bones
(Heamorrhagic diathesis) easily bleeds and frequent ecchymosis and petechiae (bruises).
Painless lymphomegaly (Enlarged lymphnodes)
Hepatospleenomegaly – can easily palpate liver and spleen due to its increased size.
Fibrosis of bone marrow
Chloroma or Leukemia Cutis or myeloid sarcoma or granular sarcoma or extramedullary myeloid tumour
Swollen painfull and bleeding gums
Cranial nerve Paralysis if CNS is involved
Increased blood cell count , WBC or RBC or Platelets, depending on type with most if the cells immature and lacking differentiation.
Complete Blood Count
Bone Marrow Biopsy
Lymph Node Biopsy
HOMEOPATHIC TREATMENT WITH INDICATED HOMEOPATHIC MEDICINES
Mycosis Fungoides is a type of Non-Hogkin Lymphoma. It is the most common type of Cutaneous T-Cell Lymphoma(CTCL).
Mycosis Fungoides is a misnomer which means “Mushroom-like fungal disease” but by no means it is a fungal condition. It is a type of blood cancer caused due to unusual expression of Skin-associated CD4 T-Cells. This cancer affects skin and produces various lesions on skin and rarely metastatise in other tissues.
It is a fatal condition with 10year survival rate of less than 70% which is even less in elderly.
It usually appears in people above 20years of age and is more common after age of 50yrs , males are affected more than females, the disease tends to be more fatal in black race. Survival rate has been found good in married white women.
Causes of Mycosis Fungoides remains unclear
No hereditary or genetic factors have been found associated to the disease.
It is considered to be non-contagious but some studies suggest that Human T-cell Lymphotropic Virus is associated with this condition.
Initially disease shows symptoms that are not distinguishing and in most of the cases it resembles psoriasis or eczema. Even on biopsy it can not be diagnosed easily in early stages. Even in later stages multiple biopies are required to establish diagnosis.
Disease presentation begins from skin as exfoliating, pruritic, erythodermic eruptions resembling to Eczema or Psoriasis and is almost always mistaken initially in most cases. These eruptions tends to appear first on buttocks in vast majority of cases and then spreads throughout the body. Pruritus is present in only 20% of all the cases. In later stages tumourous and ulcerative lesions may also appear. Disease usually in most cases starts appearing at around age of 45-50 and is a slow prohressing condition with and its usually around age of 60+ that mist patient starts presenting symptoms of later stages like tumours, generalised pruritus and erythrodrema and ulceration. Though in many cases it may start as early as age of 20 and rarely before 20yrs of age. The diseases is classified into three stages
Stages of Mycosis Fungoides
Mycosis fungoides is divided into three stages viz.
Pre Mycotic Stage
It starts appearing on skin at this stage as erythematous, pruritic, exfoliating skin eruptions.
On biopsy it cannot be diagnosed at this stage as histopsthology shows pattern of non specific dermatosis with epidermal psoriasiform changes.
In Mycotic stage Infiltrative Plaques starts appearing as slightly raises or wrinkled spots.
On histopathology polymorphs and few atypical lymphoid cells are seen inflamatory infiltrates in dermis. When this cells are seen lined up.in epidermal basal layer without spongiosis then its confirmatory finding to establish diagnosis of mycosis fungoides.
Nodular overgrowths are seen on skin ranging from few milimeters to centimeters scattered throughout the body along with plaques and patches. Usually it appears on the same place where the plaques and patches are. Also there is erosion of the tumours and ulcerations is seen in many cases over the tumour and plaques.
On histopathology they show medium sized lymphocytes with cerebroid nuclei expands dermis.
DIAGNOSIS OF MYCOSIS FUNGOIDES
Diagnosis is based primarily on histopathological findings of the skin lesions
Clinically patients showing features suggestive of or doubted mycosis fungoides are closely monitored over the time untill biopsy confirms. Multiple boipsies of various lesions might be required at every progressing stage untill confirmed, as its very difficult to estsblish diagnosis in initial stafe wether clinically or histopathologically as it resembles psoriasis or eczema.
On histopathology following findings are required to establish diagnosis of mycosis fungoides
Band-like lymphocyte infiltrate in superficial papillary dermis
Cerebroid T-cells in dermal and epidermal infiltrate
Pautriers Microabscesses – though not present in most cases but is characteristic finding of mycosis fungoides where in the epidermal infiltrate shows atypical lymphocytes arranged in aggregates of four or more.
Epilepsy is condition where in abnormal paroxysmal hyper-synchronous electrical changes within brain causes unpredictable, sudden and repetitive spells of seizures.
CAUSES OF EPILEPSY
Infections of Central Nervous System
It can be due to any structural or physiological abnormality within brain caused due to genetic mutations, injuries, infections, diseases, tumours and other unknown factors. Cause for epilepsy in many cases remains unknown.
SIGNS AND SYMPTOMS OF EPILEPSY
ICTAL STAGE OR SEIZURE
Epilepsy is caharacterised by different patterns of seizures.It is a state of sudden onset of varried degree of involuntary muscular stiffness or relaxation or combination of both with varied degree from mildly altered to complete loss in sensations and consciousness due to abnormal electrical changes within brain.
General Signs of Seizure
1)Outwardly seen signs
Complete stiffness of body due to contraction of muscles of body Or
Complete relaxation of body muscles Or
Contraction with relaxation causing twitching and jerking of body.
Suddenly losing and regaining of consciousness
Eyes turned ind fixed in one direction
Fixed, dilated or contracted pupils
Locked jaws, causing bitting of tongue between teeth, causing severe injury on tongue and bleeding.
Excessive salivation and froth from mouth
Involuntary passage of urine
2) Signs Within felt only by the patient
Strong abnormal smells
Strong emotional swings
Tingling sensation in toes and fingers
Rising sensations in abdomen
Epilepsy patient may show varried pattern of symptoms, depending upon type of seizure, which is dependent on which region of brain is involved. Below is the classification of types of seizures
Types of Seizures
I)Focal or Partial Seizures
One Hemisphere or One lobe is involved it can be classified into two types:
Simple Partial – Patient remains conscious, that is aware, realises and understands that something is happening is somewhat responsive, can recollect what had happened(during seizure), comparatively smaller region in brain is involved, patients feels strange sensations, jerking movements.
Complex Partial – Patient loses consciousness completely or loss of awareness and responsiveness, may not be able to recollect episode of seizure or what had happened then.
Both the hemisphere are involved, these type of seizures are classified into six sub-types
Atonic – Also called drop seizure or akinetic seizure. Partial or complete loss of muscle tone and control especially of trunk muscles causing patient to fall forwards with head leaning forwards causing injury. Atonic seizures usually doesnt last more than fifteen seconds in some cases followed by paralysis in a muscle group not lasting for more than three minutes. Usually the onset in most cases is during childhood and may persist into aldulthood. All the cases of concurrent Atonic seizures with onset during childhood needs to be carefully evauated for Lenox-Gustaut Syndrome (LGS) characterised by concurrent episodes of either atonic or tonic seizures with cognitive disorders and spikes on electroencephalogram. LGS a rare, complex and fatal condition usually caused due to congenital infections, genetic disorders like Tuberous Sclerosis and West Syndrome, many other genetic mutations, brain lesions. Atonic seizures are also found in Dravets Syndrome.
Tonic – Sudden stiffness due contractions of muscles of limbs and trunk causing patient to fall backwards which may result into injury due to fall, it often occurs in state of sleep as well. These type of seizures usually do not last for more than 20 minutes. Tonic seizures are one of the most commin type of seizures associatex with Lenox -Gustaut syndrome as mentioned above.
Clonic – Sustained uncontrolled violent rythmic jerking of body parts due to rapid contraction and relaxation of muscles, cant be stopped even by exerting force. This type of seizures are also refered as convuslions.
Tonic-Clonic – Tonic and Clonic pattern of seizures follows each other randomly in phases. In Tonic phase the muscles suddenly contracts and body stiffens followed by clonic phase when suddenly patient’s body starts jerking violently in rythm due to rapid contraction and relaxation of muscles.
Myoclonic – Jerking and Twitching of group of muscles. Usually patient is conscious. This type of seizures are seen in many conditions amd syndromes like LGS(mentioned above), juvenile myoclonic epilepsy (usually appears during puberty, morning seizures usually after patient wakes up usually involves neck and upper limb), Progressive Myoclonic Epilepsy(rare syndrome of combination of Tonic-Clonic and Myoclonic)etc.
Abscense – In this type patient suddenly lose conscious and soon regiains consciousness with no other evident external signs except patient suddenly stops and become stand still and visibly , for others, outwardly they seem as if lost out in thought for a while.
Secondary Generalised Seizures
Starts as partial seizure and progresses as generalised seizure. It is termed as secondary generalised seizure, as the primary event was initial partial seizure and then it progressed to generalised seizure.
When seizures fail to stop and keep continuing for more than 5 minutes, usually the seizure pattern is of Tonic-Clonic type. Its a medical emergency and may prove fatal if not treated immediately
Confussion lasting for few munuted to couple of hours.
Paralysis of limbs one sided, lasting for upto 15 hours and may take upto 2 days for complete recovery, it is called Todd’s Paralysis.
DIAGNOSIS OF EPILEPSY
And may require many other tests to find out underlying cause of epilepsy.
Usually single joint is infected, less frequently more than one joints are involved.
Most commonly involved joint is knee joint and other freqently involved joints are hip, spine, shoulder, wrist, elbow, sacroilliac and sternoclavicular joints.
Sudden onset of symptoms, fast progression of disease.
Swelling, redness with increased local Heat and pain around joint. Swelling and redness is comparatively much more than other types of arthritis.
Fever with or without chills and headache.
Cant move joint due to severe pain.
Pain aggravated in slightest motion or jarring, pain is ususally aching type with stitching, stinging and pulsating.
DIAGNOSIS OF SEPTIC ARTHRITIS
Athrocentesis – microorganisms usually found on culture, WBC count above 50,000-1,00,000/cubic mm, neutrophils more than 90%, lactate count more than 10mmol/l.
CBC – increased wbc
Blood culture positive for micro-organism
ESR – elevated
CRP – elevated
Procalcitonin – elevated
NAAT – to rule out gonorehoea
Ultrasound – joint effusion
CT scan – Region involved type and extent of damage
MRI – Region involved type and extent of damage
HOMOEOPATHIC MEDICINES FOR SEPTIC ARTHRITIS
Septic Arthritis is a medical emergeny case and requires immediate medical intervention, any delay in treatment can cause damage and complete destruction of joint with in hours to days.
Acute fast acting Homeopathic Medicines are selected with special affinity to joints and pathogenesis that of sudden, severe, acute inflamation with much swelling redness. Below is the list of indicated homeopathic medicines that I prefer in case of infective arthritis.
Dementia is a syndrome of cognitive deficits caused due to certain underlying disease conditions.
It characterised by weak memory, decreased ability to think, calculate, judge, reason, deterioration of language, difficulty in orientation of time and location, lack of initiative, emotional and behavioural problems.
CAUSES OF DEMENTIA
Dementia in most patients is secondary to one or more underlying conditions that affects Central Nervous System like certain –
Hereditary or Acquired Genetic Disorders
Below mentioned are the most common diseases that shows symptoms of dementia.
Of all the causes of dementia, Alzheimer’s Disease is present in almost 60-80% of all the cases as the underlying cause of dementia, making it the most common cause of dementia. In many patients Alzheimer’s Disease co-exists with some other condition as underlying cause of dementia.
Depending upon the underlying cause and its stage of progression it may be either
Non-Progressive or Slow-progressive or Fast-progressive
Reversible or Irreversible
Presence of number of symptoms, its appearance, sequence and intensity depends upon the underlying causative disease condition.
More or less the overall picture of dementia remains the same in various diseases only weightage to different parameter like (recall, Orientation of Time and Place, Attention and Calculation, Registration, Recall, Repetition, Language, Complex Commands) of cognitive deterioration differs a bit in different diseases and different stages. This helps in rough clinical assessment of underlying condition.
SIGNS AND SYMPTOMS
It is characterised by symptoms borne out of cognitive deficits
Forgetfulness especially recent events causing patient to misplace things and ask repeated questions, repeats phrases, difficulty in recalling names of objects or persons.
Decreased ability to think, making patient seem irrational in judging, reasoning concluding, taking decisions, initiatives
Lack of attention and difficulty in calculations makes it difficult for patient to maintain his finances.
Reduced vocubulary, causing deterioration in language.
Difficulty in orientation of time, directionality and location causing patient of getting lost frequently.
Difficulty in recognising and identifying objects due to lack of visuo-spatial articulation.
Tremors, difficulty in balancing.
Difficulty in eating especially swallowing needs liquid or thickened liquid diet.
Difficulty in daily routine, house keeping and self care.
All this above neurocognitive disorders results in emotional problems and low spirits and other neuro-psychiatric symptoms as mentioned below
Common Neuspychiatric symptoms of dementia are termed as “Behavioural and Psychological Symptoms of Dementia -BPSD” listed below
Lack of attention
Difficulty in problem solving
Initially symptoms are very difficult to notice and only close relative can judge or evaluate the signs and symptoms.
Over time these symptoms starts becoming more noticable as the patients condition starts deteriorating as the disease progresses.
The progression of disease is divided into four stages, where in, above mentioned symptoms gradually worsen in each progressive stage viz.
1)Mild Cognitive Impairment (MCI)
Scores 27-30 on MMSE scale of cognition.
No one can notice easily untill patient is evaluated.
Impairement is not so severe so as to interfere persons Activities of Daily Living (ADL).
At this stage patient is not termed as dementia patient its more of a prodromal phase
Not all but most of these patient deteriorate in cognitive deficits and progress in to Early Stage Dementia
2)Early Stage Dementia
Scores 20-25 on MMSE scale of cognition.
Only close relatives and caretaker can notice the signs and symptoms.
Difficulty in complex activity and comands.
Signs and symptoms depends much upon the underlying disease, that which symptom will be more pronounced. Eg. In dementia of Alzheimer’s Disease the memory related symptoms will be more pronounced in first stage while in dementia with lewy bodies and frontotemporal difficulty in organisation and planning will be more pronounced.
3)Mid Stage Dementia (or Moderate)
Score on MMSE scale 6-17.
Now the symptoms are noticable to everyone.
Gets confused in unfamiliar place.
Can do only simple work much difficulty in Instrumental Activities of Daily Living(IADLS).
Needs frequent reminders for everything
At these stage they have started becoming dependent and cant be left alone.
4)Late Stage Dementia (or Severe)
Sore on MMSE scale below 6.
Cannot do even Basic Activities of Daily Living(basicADLS)
Requires full-time assistance and become completely dependent cannot be left alone.
Patient cant easily recognise even close relative.
Tremors and loss of balance, may fall and injure themself.
Difficulty in identifying and handling objects in this case they might accidentally injury themself by misshandling objects.
Difficulty in eating espescially in swallowing, liquid or thickened liquid diet is prefered.
Cannot retain urine or stools and requires assistance in toilet hyegine.
Issues with appetite, sleep and behaviour.
There are many patient based/caretaker based/ combination of patient cum caretaker based questionaire tests designed to evaluate cognitive skills of patient.
These tests helps us to evaluate different parameters of cognitive skills like
Orientation of Time
Orientation of Place
Based on the score weightage of different parameters and the total score we can not only assess the grading and stage of the condition but also it gives rough differentiation on probable underlying disease that has caused dementia. Accordingly we can determine if any further investigations are required to diagnose the underlying disease.
Every tests has its own pros and cons and specificity and sensitivity. So more than one of the following test may be called in if required.
Patient Specific Tests
MMSE – Mini Mental State Examination
3MS – Modified Mini Mental State Examinations
AMTS – Abreviated Mental Test Score
CASI – Cognitive Abilities Assessment Instrument
MoCA – Montreal Cognitive Assessment
Trail Making Tests
Questionaires for Caretakers Relatives and other informants
IQCODE – Informant Questionnaire on Cognitive Decline in the Elderly
Combination of Patient specific and informant specific questionaires test
General Practitioner Assessment of Cognition
Blood tests to rule out any other anomalies like and vitamin deficiencies, hormonal imbalances, electrlyte imbalances, infections that may potentially show similar symptoms.
MRI, CT, PIB-PET, DTBZ-PET, helps diagnose some of the disease that are know to cause dementia.
Brain Biopsy to confirm the doubted underlying disease condition.
Alzheimer’s Disease (AD) is a chronic progressive neuro-degenerative disorder affecting cognitive functioning and reducing life expectancy.
AD is one of the most common cause of dementia. It accounts almost 60-70% of all dementia cases. In most cases it co-exists with other conditions as a cause for dementia.
Its estimated that there are more than 40million cases of AD world wide. It is assumed to be one of the top 3 leading causes of death in developed countries, to take its place just after heart disease and cancer.
CLASSIFICATION ALZHEIMER’S DISEASE
BASED ON AGE OF APPEARANCE – EARLY ONSET(before age of 65yrs, most of the cases are of FAD or Familial Alzheimer’s disease) or LATE ONSET(after 65yrs of age, most of them are sporadic cases)
BASED ON INHERITANCE – FAMILIAL(Familial Alzheimer’s Disease also called FAD is Autosomal-Dominant Inherent condition which in almost all cases is early onset type)or SPORADIC(not of autosomal dominant inherant type and is usually late onset type)
BASED ON INFLAMATION – INFLAMATORY or NON-INFLAMATORY
BASED ON STAGES OF DISEASE PROGRESSION– PRODROMAL, EARLY/MILD, MODERATE and SEVERE
SIGNS AND SYMPTOMS OF ALZHEIMER’s DISEASE
Alzhermer’s Disease is characterised by gradually progressing loss of cognitive functions, especially memory and other related cognitive skills like thinking and reasoning, leading to difficulty in day to day activity – like language deterioration, forgetting and misplacing thing making it difficult to independently manage house and finances, forgeting recent events, repeatedly asking same question even after getting answer, difficulty in learning and recollecting recently learnt thing, difficulty in articulating image, recognisation of objects things and beings (non-occular visuo-spatial) all this deteriorating patients skill of reasoning and executing judgement and take initiatives resulting in dependence, further triggering mood and personality disorders.
All these basic symptoms are present in general in patient which are slowly progressing and increasing in severity throughout the continuum of the disease advancement so based on symptoms and its severity AD can be divided into four stages.
STAGES OF ALZHEIMER’s DISEASE
Based on disease progression, symptoms and its severity Alzheimer’s Disease can be divided into 4 stages which are progressive worsening of symptoms in same continuum.
Its the phase of Mild Cognitive Impairment (MCI) or pre-dementia, not all cases of MCI are of AD as it can be seen in ageing and other conditions as well, so at this stage one cannot confirm AD untill patient shows other definitive signs and symptoms of AD which may take upto 8yrs to develop.
This stage shows following symptoms, which are of very mild degree and needs through neurophysiological evaluation to get detected.
Occasional problems in recollecting recent events
Occasional difficulty in exactly recollecting recently lernt facts and information
Reduced Empathy noticed on some instances
Mild changes is sense of humour
As disease progresses further the severity of symptoms of cognitive disorders of memory, thinking, reasoning increases so as to easily becoming evident and establish diagnosis of AD and excluding other condition based on slow and gradually and progressively deteriorating cognition especially in front of memory.
Cannot recollect event of forgetfulness, names of family and friends.
Reduced fluency in speaking due to difficulty in recollecting words
Difficulty grasping, learning and recollecting new facts and information. Causing minor confusions in unfamiliar simple tasks or situations.
Unnoticeable problems in execution of complex activities of daily life, like orientation and organisation of cloths on self, and fine motor activity like drawing writting etc.
Irrational, inability in making decisions.
Melancholy and despondency
Disease progressess to an extent that it starts affecting bodily functioning and day to day life to an extent that patient starts losing self confidence and starts becoming dependent on others and is now evident not only to family and his physician but also to others.
Sometimes cannot even recollect name of close family members.
Loss of vocabulary resulting in Language deterioration
Reduced coordination in complex motor sequence, needs assistance in many cases in certain complex routine tasks like wearing dress. This may even cause frequent injuries and falls.
Visuo-spatial disturbances causing difficulty in articulating image, recognisation of objects things and being causing illusionary misidentification and also delusions is seen.
Irritability, resistance to caregivers, wandering, insecurity,frequent or constant crying.
Difficulty determining their location.
Difficulty differentiating relations and designations
Lack of ability of reasoning judging and concluding.
Abusive, Cursing, paranoid, anxious
Repeats same conversation again and again.
Difficulty in speaking as can find word nor can frame sentence, speaks in few words or phrases
General exhaustion and debility with muscular atrophy making person immobile giving rise to other complications like bedsores and secondary infection.
Patients usually dies of secondary complications rather than disease itself
CAUSES OF ALZHEIMER’s DISEASE
Causes of Alzheimer’s Disease are not exactly known. It is believed to have one or more major fundamental reasons behind its pathology and pathogenesis along with multiple other factors contributing to it, in is development. With each case varing and may have the other factor more dominant than that found in the other case. Most of the hypothesis revolve around production of beta amyloid and tau protien as fundamental cause of AD.
Smoking, stress, depression, head injuries, certain CNS infections and high blood pressure are believed to increase risk in susceptible persons. Susceptibility much depends on genetics.
There are certain genes that are found to be associated but only in 5% of all the cases, head injury, depression, hypertension, smoking are also believed to be causative or contributory factors for AD.
Type, mode of onset, symptoms, its severity and specificity is determined by which and how many genes are involved and at which point there is SNP or mutations. More than 30 genes are found with more than 60 locus of SNP which are associated with Alzheimer’s Disease few of them are listed below.
Mutations in above mentioned genes causes increase in a protein called Aβ42, which forms major component of Senile Plaques in Alzheimer’s Disease.
Sporadic (Not of Autosomal-Inherant Dominant type)
APOEε4 allele – increases risk by 3 times in heterozygous and by 15 times in homozygous.
TREM2 allele have been found to increase risk of Alzheimer’s Disease by upto 3-5times as it reduces or ceases ability of leucocytes to control the amount of βAmyloid.
There are 19 Other genes found to be involved in Late Onset Alzheimer’s Disease (LOAD).
Alzheimer’s Disease is considered to be disease of Proteopathy where there is plaque deposits due ti misfolded Beta Amyloid proteins and Tau proteins in Central Nervous System which plays central role in disease pathology resulting in neurodegeneration.
There are many hypothesis trying to explain the cause and pathogenesis of Alzheimer’s Disease.
Oldest hypothesis which believes that reduced acetyle choline synthesis is the fundamental cause for Alzheimer’s Disease, based on which many drugs for AD are prepared and marketed without any significant results so its not been widely accepted.
Hypothesis states that extracellular deposits of β-amyloid is the fundamental cause behind pathogenesis of Alzheimer’s Disease.
There are many evidence to suggest that there is fundamental role of beta amyloid in development of AD.
As many genetic study shows association of amyloid related genes allele and isoforms to be major risk factors in development of AD.
Examples of allele and isoforms of genes that are associated with amyloid and are present in many patients of Alzheimer’s Disease.
Presence of Amyloid Precursor Protein gene that’s present on chromosome 21 has extra copy in people with trisomy making its expression pronounced and these people develop some features of Alzheimer’s Disease as early as 40yrs of age.
Apolipoprotein APOEε4 breaks down Amyloid but its isoforms are not that potent in breaking down of amyloid.
Allele of TREM2 reduces the activity of WBCof controling the amount of amyloid.
Also certain other factors that are related or associated to Beta Amyloid are found to be associated in development of Alzheimer’s Disease.
Beta Amyloid oligomers called Amyloid Derived Diffused Ligands (ADDL) attach to neuron surface and disrupt synaptic signals.
Presence of receptor of Amyloid oligomer, which is believed to be a misfolded three dimensional proteineceous infectious particle (prion protein).
N-AAP is fragment of AAP adjecent to its another fragment beta-amyloid. This N-AAP undergoes self destruction by binding to TNFRSF21 also called Death Receptor6 (DR6), due to ageing genome and brain the N-AAP and TNFRSF21 pathway gets disrupted and βamyliod plays complimentary role in it.
But to contradict above findings there is also the fact that the drugs that help reduce production of beta amyloid or reduce concerntration of beta amyloid have no significant impact on disease so again amyloid hypothesis is not completely accepted.
Tau proteins stabilises microtubules and are present in neurons of central nervous system and non-neuronal cells like astrocytes and oligodendrocytes.
As per tau hypothesis of pathogenesis of Alzheimer’s Disease, series of consequential pathological changes takes place post abnormalities in tau protein which starts with hyperphosphorilation of tau protein causes pairing with other threads giving rise to neurofibrillary tangles within the cell bodies evetually destroying microtubules resulting into destruction of cytoskeletal structure, causing disruption of neuronal transortation of biochemical mechanism and finally cell death.
Most of the other hypothesis revolve around production of beta amyloid and tau protien as fundamental cause of AD and are more of supportive or initiating or maintaining or risk factors that trigger fundamental pathological factor that is amyloid or tau related anomalies.
Blood Brain Barrier Hypothesis – Disturbance in integrity of blood brain barrier .
Spirochete Infection Hypothesis – Spirochete infection induced damages may further progress into AD especially by disrupting blood brain barrier
Disrupted Cellular Homeostasis of Biometals Hypothesis – It is doubted that certain ionic biometals in cells like ionic iron, copper and zinc either affect or are being affected or both by tau protein, Amyloid Precursor Protein, APOE.
Oligodendrocye Dysfunction Hypothesis – Ageing and other factors causes dysfunction of oligodendrocyes and their associated myelin, contributing to axon damage and resultant production of amyloid.
Retrogenesis Hypothesis of Barry Reisberg – This hypothesis states that certain errors in sequence of neucleotides in genome causes initiation of the reverse process of stages of neurogenesis. That is during embryogenesis the process begins with neurulation ending with myelination as final stage, just opposite to that in AD due to disturbed genetic code the reverse process is initiated that is – first demyelination, then axon death that is white matter and finally grey matter death.
Celiac Disease Association Hypothesis – Though earlier study failed to prove any relation of celiac disease with AD but more recent studies have found some link between AD and celiac disease which is under further investigation for any confirmations regarding any role.
Autoimmune Hypothesis – Autoimmune Conditions directly or indirectly affecting oligodendrocytes and myelin sheath and causing inflamatory process may trigger excessive production of amyloid production.